Bipolar Disorder Treatment - SSRI and SNRI Antidepressants

Rashmi Nemade, Ph.D. & Mark Dombeck, Ph.D.

Selective serotonin reuptake inhibitors (SSRIs) and other new antidepressants, such as buproprion and venlafaxine, are generally considered to be the first-line choices for the depressed phase of bipolar disease. Other medications such as tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs) have also entered the bipolar treatment regimen. As discussed earlier, antidepressants alone have the potential to trigger a manic episode; therefore, they are prescribed in combination with a mood stabilizing drug.

Similar to mood stabilizers, there are studies to support the use of antidepressants in between episodes. Continuous use of both antidepressant and mood stabilization treatments may keep the severe symptoms of bipolar disorder away. Specific antidepressants may not be safe for pregnant or nursing women and should be discussed with a physician.

When a neuron releases neurotransmitters across its synapse with another cell, the recipient cell receives the chemical signals on receptors and then releases them back into the synapse. About 90% of those neurotransmitter are taken up again (in a process called reuptake) by the original transmitter-releasing cell. It is thought that in depression, the recipient neuron does not take up neurotransmitters quickly enough, because of receptor problems.

SSRI is an acronym for "Selective Serotonin Reuptake Inhibitor". Serotonin is a neurotransmitter known to have an impact on mood. The class of SSRI bipolar medications is thought to exert their antidepressant effect in part by slowing down the process of serotonin reuptake. Serotonin is thus prevented from being taken up again and ends up staying in the synaptic gap longer than it normally would, gaining the chance to be recognized repeatedly by the receptors of the recipient cell. Over time, the administration of antidepressant medications is thought to influence recipient cells to grow additional receptors, further amplifying the effect.

Although SSRIs are effective treatments for depression, little is known about how SSRIs affect individuals with bipolar disorders. Despite this fact, they remain a commonly prescribed treatment for bipolar disorders.

Some common SSRIs are fluoxetine (Prozac), fluoxetine hydrochloride (Prozac Weekly), sertaline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), and citalopram (Celexa). The side effects from SSRIs are relatively mild, most commonly they are nausea, headache, insomnia, sleepiness, nervousness, tremors, increased sweating, dry mouth, and loose bowel movements. These side effects usually resolve within a few weeks of bipolar treatment. One of the most bothersome side effects is that of sexual dysfunction. For males this includes delayed orgasm and for women, a decreased sex drive. SSRIs can also be responsible for serotonin syndrome, which occurs when too much serotonin is released and results in chills, headache, diarrhea, profuse sweating, confusion, and restlessness. In this case, SSRI use is discontinued as a bipolar treatment.

Bipolar Disorder Treatment - SNRI Antidepressants

This new class of antidepressants is known as SNRIs (serotonin norepinephrine reuptake inhibitors) because they affect not only serotonin, but also norepinephrine and other neurotransmitter systems. These bipolar medications are thought to work similarly to SSRIs in that they inhibit the reuptake of neurotransmitters known to have an effect on mood at the synaptic junction.

Buproprion (Wellbutrin) is sometimes used as a first-line treatment for bipolar disorder (along side mood stabilizer medications). It is as effective as comparable SSRI treatments for combating depressive episodes, and seems to have the added benefit of lessened risk of precipitating manic episodes (compared to SSRI antidepressants). The side effect profile is often perceived as milder as well. The most common side effects of buproprion are dry mouth, constipation, headaches, and insomnia. Care must be taken when using buproprion at higher doses, as it has been known to induce seizures.

Venlafaxine (Effexor) has also been rated highly for bipolar disorder treatment, but definitive studies are lacking at this time. There is some evidence that it relieves the symptoms of depression more quickly than other bipolar medications, has fewer side effects, and can be taken in combination with other medications easily. More research is needed to solidify the role of venlafaxine in bipolar disorder treatment.

Nefazodone (Serzone) is rated as a secondary choice in bipolar treatment. In addition to serotonin reuptake inhibition, it blocks a particular type of serotonin receptor as well. Although there are no published data regarding its efficacy in bipolar disorders, it has several advantages over SSRIs, notably usefulness in relieving anxiety and severe insomnia because of its sedating effect. Unfortunately, nefazodone is a strong inhibitor of liver enzymes and should be used cautiously.

Mirtazapine (Remeron) is another second-line antidepressant choice for bipolar treatment. Like nefazodone, there are few studies that can clearly demonstrate its efficacy for bipolar treatment. It has the qualities of sedation similar to nefazodone, but has the disagreeable side effect of inducing weight gain.